In heart, fatty acids comprise the bulk of the carbon fuel for oxidative metabolism. The transport processes that translocate acyl units across the mitochondrial membrane play key roles in the integration of cytosolic and mitochondrial aspects of fatty acid oxidation. There is an absolute requirement for carnitine for the oxidation of long-chain fatty acids. Fatty acids are transported into the mitochondria as acylcarnitine derivatives in exchange for carnitine which is exported. There are three conditions in which these transport processes appear to play important roles. These are: 1). in hearts performing high levels of mechanical work, the rate of transport of long-chain acyl units limits the rate of fatty acid oxidation; 2). in aerobic hearts, the transport system for acetylcarnitine may provide an important couple between rates of acetyl-CoA oxidation in the mitochondria and rates of activation of long-chain fatty acid in the cytosol; and 3). during myocardial ischemia, a net transfer of carnitine from the cytosolic to the mitochondrial compartment occurs. The studies in this proposal are designed to elucidate the mechanisms of acyl transport, to determine the controls of the transport systems and to assess the physiological and pathological roles of these processes in the overall control of fatty acid metabolism. The isolated perfused heart will be used to study these transport systems in the intact heart. Isolated mitochondria will be used to study the translocation mechanisms and their controls in vitro. Determining the control of these transport processes may facilitate development of a metabolic and/or pharmacologic intervention designed to improve energy metabolism in various forms of cardiac disease.